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1
Mahaparea, APK, G. Srinivas, D.V. Ramanjaneyulu, et al. "Etiology, Epidemiology, Pathophysiology, Histopathology, Diagnosis, Differential Diagnosis, Treatment and Prognosis of Squamous Cell Carcinoma in Human Beings." Journal of Advancement in Immunology 2, no. 1 (2025): 1–9. https://doi.org/10.5281/zenodo.15261332.
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<em>The incidence of squamous cell carcinoma, the second most prevalent skin cancer, is steadily increasing annually, which is a serious public health problem, especially in the United States. Mortality rates for cutaneous squamous cell carcinoma are comparable to those of melanoma, renal carcinoma, and oro</em><em> pharyngeal carcinoma in the central and southern regions of the United States. Timely surveillance, early diagnosis, and prompt treatment are </em><em>crucial to minimize morbidity </em><em>as well as mortality risks. </em><em> The mainstay of therapy is still surgical excision, however new therapeutic techniques are being brought about by continuous research. </em><em> Besides, nonsurgical options, </em><em>namely radiation therapy, topical creams, cryo</em><em> therapy, photo</em><em> dynamic therapy, and laser ablation, are available, </em><em>particularly for patients unsuitable for surgery. </em><em> Whatever it may be, these nonsurgical treatments </em><em>frequently exhibit higher recurrence rates.</em> <em>In order to encourage early diagnosis and treatment, especially for high-risk patients, healthcare practitioners prefer regular follow-ups and routine skin checks. This emphasizes the significance of teamwork in providing the best possible care. A skin biopsy is typically required for diagnosis, and in more advanced instances, sentinel lymph node biopsy and further imaging are often required. Skin squamous cell carcinoma's aetiology, epidemiology, pathophysiology, histopathological subtypes, clinical characteristics, and available treatments are all covered in this activity. Due of its close ties to ultraviolet light, this activity underscores the importance of photoprotection in lowering the incidence of cutaneous squamous cell cancer. Thus, this exercise emphasises how crucial it is for healthcare professionals to work together across professional boundaries when advising patients on preventative measures, such as using SPF 30 sunscreen to avoid the sun, wearing protective clothes, and using eyewear.</em>
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Pinheiro, Jorge, Margarida Sá Fernandes, Ana Rodrigues Pereira, and José Manuel Lopes. "Histological Subtypes and Clinical Behavior Evaluation of Salivary Gland Tumors." Acta Médica Portuguesa 31, no. 11 (2018): 641. http://dx.doi.org/10.20344/amp.9023.
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Introduction: Salivary gland tumors include a wide spectrum of histological subtypes and clinical behavior, which we aim to evaluate.Material and Methods: We performed a retrospective study of all salivary gland tumors diagnosed and treated at the Centro Hospitalar São João, Porto, between 2005 and 2015. Histological re- evaluation was performed in all cases and patient files were reviewed and both clinical and follow-up data were collected. Disease-free survival and overall survival were evaluated using Kaplan-Meier survival curves and compared using the Mantel-Cox log-rank test. The significance threshold was set at 0.05.Results: We selected 295 cases, 150 males with a mean age at diagnosis of 50.4 (± 16.4) years. Primary benign epithelial tumors [n = 228 (77.3%)] were mostly pleomorphic adenomas [n = 148 (64.9%)] and Warthin tumors [n = 61 (26.8%)]. Primary malignant epithelial tumors [n = 43 (14.8%)] included mucoepidermoid [n = 16 (37.2%)], adenoid cystic [n = 6 (14.0%)] and acinic cell [n = 5 (11.6%)] carcinomas; 32 (74.4%) in parotid, 2 (4.6%) in submandibular and 9 (21%) in minor salivary glands. Primary epithelial tumors were more frequently malignant in minor (33.3%) than in major (13.9%) salivary glands. Local recurrence occurred in 30.2% and distant metastases in 25.6% tumors. The mean disease-free interval was 26 (± 37.5) months; most metastases were in lung and central nervous system. The 5 and 10 year disease-free survival rates were 63.4% and 50.1%, respectively; the 5 and 10 year disease-specific survival rates were 76.9% and 57.9%, respectively. Primary salivary tumors included also lymphomas [n = 8 (2.7%)] and soft tissue tumors [n = 5 (1.7%)]. Secondary tumors included metastases of carcinomas [n = 7 (2.4%)] and involvement by lymphoma [n = 1 (0.3%)].Discussion: Our results concerning age, gender, histological subtype, frequency and clinical behavior of salivary tumors concur with European studies. Divergence with Portuguese studies might be related with the inclusion criteria, clinical referral and time lag variations.Conclusion: Although uncommon, salivary gland tumors occur in a wide age range and include histological subtypes with diverse prognosis.
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Zulfiqar, Muhammad I., Dennis D. Weisenburger, Fausto R. Loberiza, et al. "The Impact of Histological Subtypes on Outcome in Patients with Mantle Cell Lymphoma Treated with or without Autologous Stem Cell Transplant." Blood 110, no. 11 (2007): 1904. http://dx.doi.org/10.1182/blood.v110.11.1904.1904.
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Abstract Mantle cell lymphoma (MCL) accounts for 7% of all non-Hodgkin’s lymphomas, with median overall survival in most series of 3–4 years. MCL has been classified into three histological subtypes which include diffuse MCL, nodular MCL, and blastic MCL. A relatively small number of studies have examined the prognostic importance of histology in MCL. The aim of this study was to determine if the progression free survival (PFS) and overall survival (OS) rates in mantle cell lymphoma differ among histological subtypes. A total of 102 patients with MCL, treated by the Nebraska Lymphoma Study Group between January 1986 and June 2006, with a median age of 60 years (range 32–89 years) were available for study. Patients were treated with HyperCVAD or a CHOP like regimen with or without rituximab and autologous hematopoetic stem cell transplant (ASCT). All cases were confirmed using cyclin D1 staining. Regardless of treatment, our study failed to show a significant difference in PFS (p=0.26) or OS (P=0.06) among histological subtypes. There was a trend for better survival in patients with nodular MCL. However, in patients receiving ASCT, there was a significantly higher PFS (P=0.0001) and OS (p=0.0005) compared to patients not receiving ASCT. The 3 year PFS for patients receiving HyperCVAD followed by ASCT was 64% compared to the 3 year PFS for HyperCVAD alone of 0 (p=0.008). In conclusion, we failed to show association between histological subtypes of MCL with outcomes regardless of treatment. However, the use of ASCT improved survival.
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Rafael Vivas, Mauro. "Exophytic Soft Tissue Sarcoma Versus Cutaneous Carcinoma. A Challenge in Orthopedic Oncology. Case Report." Clinical Orthopaedics and Trauma Care 5, no. 4 (2023): 01–04. http://dx.doi.org/10.31579/2694-0248/043.
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Soft tissue sarcomas (SPB) are heterogeneous tumors of mesenchymal origin that include more than 100 different subtypes. The great histological variability and its infrequency make diagnosis a challenge, as shown by the series of 1463 patients with sarcomas by Ray-Coquard et al., carried out in 2016 with a lack of concordance of 43%.
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Cserni, Gábor, Cecily M. Quinn, Maria Pia Foschini, et al. "Triple-Negative Breast Cancer Histological Subtypes with a Favourable Prognosis." Cancers 13, no. 22 (2021): 5694. http://dx.doi.org/10.3390/cancers13225694.
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Triple-negative breast cancers (TNBC), as a group of tumours, have a worse prognosis than stage-matched non-TNBC and lack the benefits of routinely available targeted therapy. However, TNBC is a heterogeneous group of neoplasms, which includes some special type carcinomas with a relatively indolent course. This review on behalf of the European Working Group for Breast Screening Pathology reviews the literature on the special histological types of BC that are reported to have a triple negative phenotype and indolent behaviour. These include adenoid cystic carcinoma of classical type, low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, low-grade mucoepidermoid carcinoma, secretory carcinoma, acinic cell carcinoma, and tall cell carcinoma with reversed polarity. The pathological and known molecular features as well as clinical data including treatment and prognosis of these special TNBC subtypes are summarised and it is concluded that many patients with these rare TNBC pure subtypes are unlikely to benefit from systemic chemotherapy. A consensus statement of the working group relating to the multidisciplinary approach and treatment of these rare tumour types concludes the review.
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Blay, Jean-Yves. "Treatment of advanced soft tissue sarcoma by histological subtype: wish, prediction or reality?" Future Oncology 15, no. 26s (2019): 5–10. http://dx.doi.org/10.2217/fon-2019-0488.
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Soft tissue sarcomas (STS) are heterogenous cancers encompassing more than 100 histological and molecular subtypes. Their extreme rarity underscores the need for international collaboration to identify specific treatment protocols. Increasing knowledge of STS complexity as defined by molecular biology has led to the introduction of targeted therapies for several sarcoma subtypes, which is an encouraging start. In advanced STS, doxorubicin-based regimens are standard first-line chemotherapy. Options for second and later lines include ifosfamide, trabectedin, pazopanib, eribulin and gemcitabine-based regimens. Histological subtype has become a key factor when selecting best options to treat advanced sarcoma; however, the challenges of identifying optimal treatments for all STS histotypes are undeniably formidable. Fortunately, the sarcoma community shares the common goal of seeking greater knowledge about the characteristics of each subtype in order to improve diagnosis and outcomes. Progress made to date in this regard suggests that the vision to treat by subtype is achievable.
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Mastromarino, Maria Giovanna, Alessandra Lenzini, Vittorio Aprile, et al. "New Insights in Pleural Mesothelioma Classification Update: Diagnostic Traps and Prognostic Implications." Diagnostics 12, no. 12 (2022): 2905. http://dx.doi.org/10.3390/diagnostics12122905.
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The 2021 WHO Classification of Tumors of the Pleura has introduced significant changes in mesothelioma codification beyond the three current histological subtypes—epithelioid, sarcomatoid and biphasic. Major advances since the 2015 WHO classification include nuclear grading and the introduction of architectural patterns, cytological and stromal features for epithelioid diffuse mesothelioma. Mesothelioma in situ has been recognized as a diagnostic category. Demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH, is valuable in establishing the diagnosis of epithelioid mesothelioma. Recent emerging data proved that grading and histological subtypes have prognostic implications and may be helpful to patient risk stratification and clinical management. Nevertheless, the latest mesothelioma classification increases the already non-negligible diagnostic pitfalls, especially concerning differential diagnosis of pre-invasive tumors. In this review, recent changes in histologic classification of mesothelioma and advances in molecular markers are presented and their relation to diagnostic challenges and prognostic implications is discussed.
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Alimohamed, Saif, James I. Geller, and Bruce Aronow. "TCGA Kidney Cell Atlas: A differential gene expression database for the dissection of tumor-specific gene modules." Journal of Clinical Oncology 38, no. 15_suppl (2020): e17078-e17078. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e17078.
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e17078 Background: The Cancer Genome Atlas project has become a leading source for data that has allowed the identification of a broad range of human cancer tumor types and subtypes and has revealed deep complexity with respect to the differentiation, or lack thereof, among human cancers. In particular, differential gene expression analyses have revealed a wealth of active oncogenic pathways, underlying gene mutation drivers, discriminative markers, and candidate therapeutic targets. Despite its rich composition, several factors have led to it not attaining the utility it would seem to offer. Methods: To study this, we dissected molecular subtypes in the TCGA and used the Pan-Kidney (n = 1022 samples) Portion within it to determine where obstacles seem to limit its utility. We re-clustered the renal carcinomas to create more appropriate histology annotations for these samples. The molecular subtypes were then found through K-means using differentially expressed known developmental regulators per histological annotation. After deriving these new annotations, the histology and molecular subtypes were compared to one another via T-test to generate gene modules that characterize these classes/subclasses. Results: We identified a number of factors that include inconsistent metadata attributes, apparent misclassification of histological subtypes, and molecular subtypes that do not match with that obtained by focused approaches to rederive principle subclasses. Our gene modules showed a molecular subtype of clear cell renal carcinoma that was enriched for vascular development and nephron development. In general, the clear cell renal carcinoma and papillary renal cell carcinoma cohorts both showed significant co-expression with atlases that were enriched for genes involved in kidney development. Conclusions: Our atlas highlights the limitations of the current TCGA atlas and provides another tool to capture the rich insights from the TCGA repository through the efforts explained above, highlighted by its use in kidney carcinoma.
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Vorster, Trudie, Julian Mthombeni, Jim teWaterNaude, and James Ian Phillips. "The Association between the Histological Subtypes of Mesothelioma and Asbestos Exposure Characteristics." International Journal of Environmental Research and Public Health 19, no. 21 (2022): 14520. http://dx.doi.org/10.3390/ijerph192114520.
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Asbestos mining operations have left South Africa with a legacy of asbestos contamination and asbestos-related diseases continue to be a problem. The large-scale mining of three types of asbestos presents a unique opportunity to study malignant mesothelioma of the pleura (mesothelioma) in South Africa. This study aimed to describe the demographics of deceased individuals diagnosed with mesothelioma and explore any associations between the histological morphology of mesothelioma and asbestos characteristics. We reviewed the records of all deceased miners and ex-miners from the Pathology Automation System (PATHAUT) database of the National Institute of Occupational Health (NIOH) that were histologically diagnosed with mesothelioma in the period from January 2006–December 2016 (11 years). The study population does not include all cases of mesothelioma in South Africa but rather those that reached the compensation system. Crocidolite asbestos fibres were identified in the majority of mesothelioma cases (n = 140; 53.4%). The epithelioid subtype was most commonly present in both occupational and environmental cases. Cases with the sarcomatous subtype were older at death and fewer female cases were diagnosed with this subtype. No relationship between mesothelioma subtype and asbestos type or asbestos burden or fibre size was established.
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Cheung, Alison, Sidrah Shah, Jack Parker, et al. "Non-Epithelial Ovarian Cancers: How Much Do We Really Know?" International Journal of Environmental Research and Public Health 19, no. 3 (2022): 1106. http://dx.doi.org/10.3390/ijerph19031106.
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Non-epithelial ovarian cancers (NEOC) are a group of uncommon malignancies that mainly includes germ cell tumours (GCT), sex cord-stromal tumours (SCST), and some extremely rare tumours, such as small cell carcinomas and sarcomas. Each of these classifications encompasses multiple histologic subtypes. The aetiology and molecular origins of each sub-group of NEOC require further investigation, and our understanding on the genetic changes should be optimised. In this article, we provide an update on the clinical presentation, pathology, genetics, treatment and survival of the main histological subtypes of the GCT and the SCST, as well as of ovarian small cell carcinomas. We also discuss miRNA expression profiles of NEOC and report the currently active clinical trials that include NEOC.
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Langer, Seppo W., Lene Ringholm, Christine I. Dali, et al. "Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor: A Presentation of Two Cases." Case Reports in Medicine 2015 (2015): 1–4. http://dx.doi.org/10.1155/2015/265786.
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Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden Syndrome that were diagnosed with pulmonary carcinoids.
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Falodia, Sushil, Govind K. Makharia, J. Sateesh, Vaishali Deo, MS Tevatia, and Siddhartha Datta Gupta. "Spectrum of microscopic colitis in a tertiary care centre in India." Tropical Gastroenterology 28, no. 3 (2007): 121–25. https://doi.org/10.4103/trog_20072803_121.
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Introduction: The incidence of microscopic colitis has recently increased. Although collagenous colitis and lymphocytic colitis are the two main subtypes of microscopic colitis, many patients may not fit into either category and are thus included under the header nonspecific colitis. Of late, the spectrum of microscopic colitis has widened to include minimal change colitis, microscopic colitis not otherwise specified and microscopic colitis with giant cells. There is a lack of information concerning the spectrum of microscopic colitis in Asia. Method: In a retrospective analysis, case records of 29 patients diagnosed with microscopic colitis between1999– 2005 were analysed. Drug use parasitic infection and common bacterial infections were excluded. Colonoscopic/ sigmoidoscopic examination was done and multiple colonic mucosal biopsies were stained serially with haematoxylin and eosin for detailed histological examination and Masson trichrome for sub-epithelial collagen band. Based on histological criteria, patients were categorised into five subtypes: collagenous colitis (presence of collagenous thickening of surface epithelium basement membrane >10 μm), lymphocytic colitis (intra-epithelial lymphocytes more than 20 per 100 colonocytes), minimal change colitis (crypt architectural abnormality in the form of cryptitis and crypt dilatation in the absence of increase in intraepithelial lymphocytes and subepithelial collagenous band), microscopic colitis not otherwise specified (increased inflammatory cell infiltrates in the lamina propria in the absence of other abnormalities) and microscopic colitis with giant cells. Results: Mean age of patients was 38.59 years (range 12– 62). Of 29 patients with microscopic colitis, 7 (24.1%), 4 (13.8%), 7 (24.1%) and 11 (37.9%) were classified as collagenous colitis, lymphocytic colitis, minimal change colitis and microscopic colitis not otherwise specified, respectively. None of these patients had giant cells. There was no significant correlation between disease type and clinical manifestations. Conclusion: Microscopic colitis has a wide histological spectrum. Cases reported as non-specific colitis, may be categorised into definite subtypes of microscopic colitis.
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Sambri, Andrea, Emilia Caldari, Michele Fiore, et al. "Margin Assessment in Soft Tissue Sarcomas: Review of the Literature." Cancers 13, no. 7 (2021): 1687. http://dx.doi.org/10.3390/cancers13071687.
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Adequacy of margins must take into consideration both the resection margin width (quantity) and anatomic barrier (quality). There are several classification schemes for reporting surgical resection margin status for soft tissue sarcomas (STS). Most of the studies regarding treatment outcomes in STS included all histologic grades and histological subtypes, which include infiltrative and non-infiltrative subtypes and are very heterogeneous in terms of both histologic characteristics and treatment modalities (adjuvant treatments or not). This lack of consistency makes it difficult to compare results from study to study. Therefore, there is a great need for evidence-based standardization concerning the width of resection margins. The aim of this narrative review is to provide a comprehensive assessment of the literature on margins, and to highlight the need for a uniform description of the margin status for patients with STS. Patient cases should be discussed at multidisciplinary tumor boards and treatments should be individualized to clinical and demographic characteristics, which must include also a deep knowledge of specific histotypes behaviors, particularly infiltrative ones.
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Yoon, Hee Mang, Sun-ju Byeon, Jae-Yeon Hwang, et al. "Sacrococcygeal teratomas in newborns: a comprehensive review for the radiologists." Acta Radiologica 59, no. 2 (2017): 236–46. http://dx.doi.org/10.1177/0284185117710680.
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Sacrococcygeal teratomas are the most common solid tumor in newborn infants. The diagnosis is not difficult in many cases; however, there should be additional information on imaging studies in order to manage those infants properly. Details include histology, morphologic classification, complications such as rupture, bleeding, and mass effects on the adjacent structures. Although imaging features cannot accurately predict the histologic subtypes of the tumors, thorough evaluation of the imaging features can help distinguish malignant tumors from benign tumors. In this article, pathogenesis, histological characteristics, clinical considerations, and morphologic characteristics will be discussed.
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Galappaththi, Sapthala P. Loku, Kelly R. Smith, Enas S. Alsatari, et al. "The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences." International Journal of Molecular Sciences 25, no. 23 (2024): 13165. https://doi.org/10.3390/ijms252313165.
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Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer’s histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer’s current diagnostics and treatment modalities.
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Nappo, Gennaro, Niccola Funel, Virginia Laurenti, et al. "Ampullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour—State of the Art and Perspectives." Current Oncology 30, no. 7 (2023): 6996–7006. http://dx.doi.org/10.3390/curroncol30070507.
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There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant morphological–molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.
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Kim, Jun-Ho, and Seul Ki Lee. "Classification of Chondrosarcoma: From Characteristic to Challenging Imaging Findings." Cancers 15, no. 6 (2023): 1703. http://dx.doi.org/10.3390/cancers15061703.
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Chondrosarcomas can be classified into various forms according to the presence or absence of a precursor lesion, location, and histological subtype. The new 2020 World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone classifies chondrogenic bone tumors as benign, intermediate (locally aggressive), or malignant, and separates atypical cartilaginous tumors (ACTs) and chondrosarcoma grade 1 (CS1) as intermediate and malignant tumors. respectively. Furthermore, the classification categorizes chondrosarcomas (including ACT) into eight subtypes: central conventional (grade 1 vs. 2–3), secondary peripheral (grade 1 vs. 2–3), periosteal, dedifferentiated, mesenchymal, and clear cell chondrosarcoma. Most chondrosarcomas are the low-grade, primary central conventional type. The rarer subtypes include clear cell, mesenchymal, and dedifferentiated chondrosarcomas. Comprehensive analysis of the characteristic imaging findings can help differentiate various forms of chondrosarcomas. However, distinguishing low-grade chondrosarcomas from enchondromas or high-grade chondrosarcomas is radiologically and histopathologically challenging, even for experienced radiologists and pathologists.
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Shah, Preena, Qingmei Feng, Barbara Carey, et al. "Actinic cheilitis: guidance on monitoring and management in primary care." Journal of Oral Medicine and Oral Surgery 29, no. 3 (2023): 30. http://dx.doi.org/10.1051/mbcb/2023029.
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Actinic cheilitis is an oral potentially malignant disorder caused by UV radiation leading to damage to epithelial keratinocytes of the lips. It predominantly affects the vermillion border of the lower lip. Due to its association with chronic UV exposure, associated risk factors include geographic areas, outdoor occupations, and skin subtypes. A high proportion of lip squamous cell carcinomas arise from actinic cheilitis lesions, with histological examination usually showing a degree of dysplasia. This paper aims to review the existing literature regarding the clinical picture of actinic cheilitis, its prevalence, differential diagnoses, and consensus on management, for the education of the general dental practitioner in identifying and surveillance of this lesion.
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Agarwal, Sonika, Kathleen M. Schmeler, Pedro T. Ramirez, et al. "Outcomes of Patients Undergoing Radical Hysterectomy for Cervical Cancer of High-Risk Histological Subtypes." International Journal of Gynecologic Cancer 21, no. 1 (2011): 123–27. http://dx.doi.org/10.1097/igc.0b013e3181ffccc1.
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Background:The most common types of cervical cancer are squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma, referred to here collectively as SA cervical cancer. Other types of cervical cancer, referred to here collectively as nonsquamous/nonadenocarcinoma (NSNA) cervical cancer, include neuroendocrine, small cell, clear cell, sarcomatoid, and serous tumors. Anecdotally, NSNA tumors seem to have a worse prognosis than their SA counterparts. We sought to determine whether patients with early-stage NSNA have a worse prognosis than those with early-stage SA cervical cancer.Methods:We retrospectively reviewed charts of women with stage IA1-IB2 NSNA cervical cancer treated by radical hysterectomy and lymph node staging at M. D. Anderson Cancer Center from 1990 to 2006. The NSNA patients were matched 1:2 to patients with grade 3 SA lesions on the basis of stage, age at diagnosis, tumor size, and date of diagnosis.Results:Eighteen patients with NSNA primary cervical cancer subtypes (neuroendocrine [n = 7], small cell [n = 5], clear cell [n = 4], papillary serous [n = 1], and sarcomatoid [n = 1]) were matched to 36 patients with grade 3 SA lesions. There were no differences between the 2 groups in age, body mass index, clinical stage, or lesion size. The 2 groups also did not differ with respect to number of nodes resected, lymphovascular space invasion, margin status, lymph node metastasis, or adjuvant radiation therapy or chemotherapy. At a median follow-up of 44 months, median progression-free and overall survivals had not been reached; however, both progression-free survival (P= 0.018) and overall survival (P= 0.028) were worse for the NSNA group. The 5-year progression-free and overall survival rates were 61.2% and 67.6%, respectively, for the NSNA group, compared with 90.1% and 88.3%, respectively, for the SA group.Conclusions:Patients with early-stage NSNA cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy have a worse prognosis than patients with grade 3 SA lesions. Patients with NSNA tumors may require a multimodality approach to their cancer care.
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Metze, Dieter, Heiko Traupe, and Kira Süßmuth. "Ichthyoses—A Clinical and Pathological Spectrum from Heterogeneous Cornification Disorders to Inflammation." Dermatopathology 8, no. 2 (2021): 107–23. http://dx.doi.org/10.3390/dermatopathology8020017.
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Ichthyoses are inborn keratinization disorders affecting the skin only (non-syndromic) or are associated with diseases of internal organs (syndromic). In newborns, they can be life-threatening. The identification of the gene defects resulted in reclassification and a better understanding of the pathophysiology. Histopathologic patterns include orthohyperkeratosis with a reduced or well-developed stratum granulosum, hyperkeratosis with ortho- and parakeratosis with preserved or prominent stratum granulosum, and epidermolytic ichthyosis. Another pattern features “perinuclear vacuoles and binucleated keratinocytes”, which is associated with keratin mutations. Some ichthyoses are histologically defined by psoriasis-like features, and distinct subtypes show follicular hyperkeratosis. In addition to histological and immunohistochemical methods, these patterns allow a better histopathologic diagnosis.
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Fatima, Ghulam, Muhammad Rahil Khan, Riyasat Ahmed Memon, Zahid Ali, Osheen Vandana, and Rehan Akhtar. "Prevalence of Luminal A, Luminal B, HER2 enriched and triple negative breast carcinoma in population of Sindh." International journal of health sciences 7, S1 (2023): 1988–98. http://dx.doi.org/10.53730/ijhs.v7ns1.14443.
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The incidence of breast cancer has increased significantly in Asian countries in comparison to Western countries, and it is now one of the leading causes of cancer-related death among women worldwide. Each year, 1.5 million women (25% of all cancer women) are diagnosed with BC around the world, and this number is expected to rise to 2.2 million by 2025. In particular, breast cancer shows biologic heterogeneity in terms of risk factors, natural histories, responses to therapy, and prognostic features that vary considerably between ethnic and geographical groups. Many studies have focused on the distinctions between tumor subtypes because of the importance they play in guiding therapeutic decision making in breast cancer. These factors include histological grade, tumor type and size, and the presence of lymph node metastasis. As a proxy for profiling gene expression, immunohistochemical examination of breast cancer tissue with various biomarkers is employed. This method is cheap, widely accessible, reliable, and technically not demanding. The purpose of this research was to analyze the relationship between molecular subtypes of breast cancer and certain pathological characteristics.
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Zhai, Jing. "Non-Urothelial Malignancy in Urine Cytology." CMAS Journal 1 (April 25, 2024): 5. http://dx.doi.org/10.25259/cmasj_04_05.
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Non-urothelial malignancies of the urinary bladder are relatively rare and can be classified into primary and secondary malignancies. The histological subtypes of non-urothelial malignancy include non-urothelial carcinoma, sarcoma, lymphoma, and melanoma. The common types of primary non-urothelial carcinoma are pure squamous cell carcinoma, adenocarcinoma, and small cell carcinoma. Most primary sarcomas of the urinary bladder are leiomyosarcoma and rhabdomyosarcoma. Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue origin and diffuse large B-cell lymphoma (DLBCL) are the common primary lymphomas of the urinary bladder. Most secondary tumors of the urinary bladder result from the direct extension of adjacent organs such as the colon/rectum, prostate, and cervix. Hematogenous metastasis from other primary cancers such as breast, stomach, lung, and skin (melanoma) are less common. The cytologic diagnosis of non-urothelial malignancies is challenging due to the significant cytomorphologic overlap with high-grade urothelial carcinoma, its divergent differentiation, and subtypes. Awareness of these diagnostic entities is helpful for accurate diagnosis, especially when encountering urine specimens with unusual cytomorphology.
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Ponomarev, V. E., S. B. Polikarpova, N. I. Mehtieva, N. U. Shagina, Y. V. Vishnevskaja, and V. V. Selivanova. "Primary operable breast cancer: molecular subtypes and morphological prognostic factors." Sechenov Medical Journal 10, no. 2 (2019): 5–13. http://dx.doi.org/10.47093/22187332.2019.2.5-13.
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Aim. To study the immediate and long - term results of treatment of patients with a primary operable breast cancer, depending on the morphological and biological characteristics of the tumor. Materials and methods. The retrospective study included 974 patients aged from 30 to 82 years (a mean age of54.5 years) with a primary operable breast cancer (T1-2N0-1M0) observed from 2005 to 2012. The overall survival (OS) and disease - free survival (DFS) were studied depending on the histological type, molecular - biological subtype of breast cancer, axillary status, lymphovascular invasion, tumor histologic grade, proliferation index (by Ki-67 staining) and HER2 protein expression. Statistical data processing included a comparison of the frequencies of the studied traits, analysis of survival curves by the Kaplan-Meier method.Results. Indicators of a 5-year OS and 5 and 10-year OS and DFS were lower in carcinomas of mixed type compared with invasive carcinoma of no special type ( p =0.03) and invasive lobular carcinoma ( p =0.01). In the absence of metastases in regional lymph nodes, indicators of 5 and 10-year OS were higher compared with the macrometastatic involvement of one ( p =0.02) or two or more lymph nodes ( p =0.004): 96.0% and 89.3%; 95.4% and 79.0%; 88.9% and 79.3%, respectively. A similar trend has been noted for indicators of 5 and 10-year DFS. The OS in the absence of metastases in the lymph nodes was greater with the luminal B HER2-positive subtype and triple - negative breast cancer. The degree of malignancy of the tumor had no effect on OS. The probability of disease recurrence was significantly higher in patients with a degree of G3 compared with G1 ( p =0.00001) and G2 ( p =0.002): the rates of 5 and 10-year - old DFS were: 84.8 and 55.0%; 94.1 and 86.0%; 88.9 and 72.2%, respectively. The expression of HER2 and Ki-67 proliferation index influenced the DFS without affecting the OS.Conclusions. The morphological factors deteriorating the OS and DFS of patients with primary operable breast cancer are the presence of macrometastases in regional lymph nodes, the defeat of two or more lymph nodes, the presence of lymphovascular invasion, mixed histological form of breast cancer. The subtypes with a more aggressive course include: HER2-positive tumors, triple negative breast cancer.
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Tateo, Valentina, Lisa Manuzzi, Claudia Parisi, et al. "An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances." Pharmaceuticals 14, no. 4 (2021): 316. http://dx.doi.org/10.3390/ph14040316.
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Thymic tumors are a group of rare mediastinal malignancies that include three different histological subtypes with completely different clinical behavior: the thymic carcinomas, the thymomas, and the rarest thymic neuroendocrine tumors. Nowadays, few therapeutic options are available for relapsed and refractory thymic tumors after a first-line platinum-based chemotherapy. In the last years, the deepening of knowledge on thymus’ biological characterization has opened possibilities for new treatment options. Several clinical trials have been conducted, the majority with disappointing results mainly due to inaccurate patient selection, but recently some encouraging results have been presented. In this review, we summarize the molecular alterations observed in thymic tumors, underlying the great biological differences among the different histology, and the promising targeted therapies for the future.
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Zarzycka, Marta, Marcelina Sikora, Ines Plewniok, et al. "Understanding of Eosinophilic Esophagitis in Children - A Comprehensive Study on Epidemiology, Clinical Manifestations, Diagnosis and Innovative Treatment Modalities." Journal of Education, Health and Sport 55 (January 29, 2024): 137–54. http://dx.doi.org/10.12775/jehs.2024.55.009.
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Introduction:
 In the late 1960s, probable cases of eosinophilic esophagitis (EoE) emerged, initially linked to esophageal rings and congenital causes or gastroesophageal reflux disease (GERD). Doubts about the GERD association arose due to poor responses to antisecretory therapy. EoE is now a significant pediatric health concern, impacting 1 to 7 cases per 10,000 children.
 Purpose of the Study:
 This study aims to comprehensively explore EoE's epidemiology, etiology, subtypes, clinical manifestations, diagnostic methods, and treatment modalities.
 Materials and Methods:
 The study employs a cross-sectional analysis of pediatric EoE patients, utilizing endoscopic evaluation and histological assessment. Three distinct EoE subtypes are identified based on pathogenic characteristics. Clinical manifestations, diagnostic methods, and treatments, including endoscopy, are examined.
 Results:
 Clinical manifestations span a broad spectrum in the pediatric population. Diagnostic methods include endoscopy, esophageal manometry, impedance-pH monitoring, capsule endoscopy, and string tests. Three distinct EoE subtypes are identified with unique characteristics. Treatment modalities involve dietary management, proton pump inhibitors, topical corticosteroids, biologic therapies, allergen immunotherapy, and endoscopic interventions.
 Conclusion:
 Formerly associated with GERD, EoE is now a significant pediatric health concern. The study underscores the importance of comprehensive diagnostic approaches and diverse treatment modalities, including promising biologic therapies and allergen immunotherapy. Understanding these aspects is crucial for effective management and improved outcomes in patients.
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Swed, Brandon, Omar Gandarilla, Kenrry Chiu, et al. "Rare Histological Variants of Liver Cancer and Their Management: A Single-Institution Experience." Case Reports in Hepatology 2021 (April 21, 2021): 1–7. http://dx.doi.org/10.1155/2021/6654229.
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Primary liver malignancies, including hepatocellular carcinoma (HCC) and cholangiocarcinoma, are a major cause of cancer-related morbidity and mortality worldwide. There are several histologically and biologically distinct subtypes of liver cancer that have previously been reported. However, literature regarding the nonsurgical management of these patients upon disease recurrence remains limited. These variants include combined HCC-cholangiocarcinoma (cHCC-CC), Epstein–Barr virus- (EBV-) associated carcinoma, undifferentiated carcinoma, and clear cell or thyroid-like variants of HCC. Here, we aim to highlight the pathologic features, clinical course, and outcomes of five patients with these unusual hepatic tumors and explain the rationale behind the choice of their systemic therapies upon disease recurrence. All patients underwent surgical resection as the standard of care for localized disease, and upon relapse, they were treated with either chemotherapy, targeted therapy, immunotherapy, or active surveillance based on the clinical context and tumor histology. These rare variants are important to recognize as they have prognostic and therapeutic implications, and there are currently insufficient data in the literature to guide further therapy.
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Franco, Paolo Niccolò, Federica Vernuccio, Cesare Maino, Roberto Cannella, Milagros Otero-García, and Davide Ippolito. "Radiomics in Gynaecological Imaging: A State-of-the-Art Review." Applied Sciences 13, no. 21 (2023): 11839. http://dx.doi.org/10.3390/app132111839.
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Radiomics is an emerging field of research based on extracting mathematical descriptive features from medical images with the aim of improving diagnostic performance and providing increasing support to clinical decisions. In recent years, a number of studies have been published regarding different possible applications of radiomics in gynaecological imaging. Many fields have been explored, such as tumour diagnosis and staging, differentiation of histological subtypes, assessment of distant metastases, prediction of response to therapy, recurrence, and patients’ outcome. However, several studies are not robust, do not include validation cohorts, or lack reproducibility. On these bases, the purpose of this narrative review is to provide an overview of the most relevant studies in the literature on radiomics in gynaecological imaging. We focused on gynaecological malignancies, particularly endometrial, cervical, mesenchymal, and ovarian malignant pathologies.
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De Lauretis, Flavia, Alejandro Martin Sanchez, Cristina Accetta, et al. "Malignant Mesenchymal Tumors of the Breast: Current Challenges and New Perspectives on Primary Sarcomas and Malignant Phyllodes Tumors." Life 15, no. 4 (2025): 673. https://doi.org/10.3390/life15040673.
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Mesenchymal tumors of the breast constitute a rare and heterogeneous group of neoplasms, representing only 0.5% to 1% of all breast tumors. Originating from mesenchymal tissues, these tumors include various histological subtypes. They are particularly aggressive, characterized by a high propensity for local recurrence and an overall poor prognosis. The rarity of these cases has impeded the development of comprehensive clinical studies, leading to a lack of standardized diagnostic protocols and treatment guidelines. This review provides a thorough synthesis of current knowledge on breast mesenchymal tumors with a specific focus on malignant variants such as phyllodes tumors and breast sarcomas. It also addresses the diagnostic challenges faced by clinicians, evaluates current therapeutic strategies, and emphasizes the crucial role of surgical treatment. Additionally, it examines the evolving roles of chemotherapy and radiotherapy in enhancing patient outcomes.
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Babaier, Abdulaziz, Hanan Mal, Waleed Alselwi, and Prafull Ghatage. "Low-Grade Serous Carcinoma of the Ovary: The Current Status." Diagnostics 12, no. 2 (2022): 458. http://dx.doi.org/10.3390/diagnostics12020458.
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Low-grade serous carcinoma (LGSC) of the ovary is a rare histological subtype of epithelial ovarian carcinoma. It has distinct clinical behavior and a specific molecular profile. Compared with high-grade serous carcinoma, this tumor presents at a younger age, has an indolent course, and is associated with prolonged survival. LGSC can arise de novo or originate following a serous borderline tumor (SBT). Pathological differentiation between LGSC and other ovarian carcinoma histological subtypes is fundamental. Several factors might influence the overall outcome, such as the age at diagnosis, current smoking, elevated body mass index, mutational status, hormonal receptors’ expression, and Ki-67 proliferation index. Surgery is the main treatment option in LGSC, and efforts must be maximized to achieve a microscopic residual in metastatic disease. Despite being relatively chemo-resistant, adjuvant platinum-based chemotherapy remains the standard of care in LGSC. Hormonal maintenance therapy after adjuvant chemotherapy results in improved outcomes. Treatment options for disease recurrence include secondary cytoreductive surgery, chemotherapy, hormonal therapy, targeted therapy, and clinical trials. Advancements in genomic studies and targeted therapies are expected to change the treatment landscape in LGSC.
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Olazo Cárdenas, Kamyla Mychele, Juan Carlos Zea Burga, Gabriel De La Cruz Ku, and Ramiro Fernández. "Gallbladder cancer at a tertiary referral hospital in Peru: characteristics and outcomes in 20 years’ experience." ACTA MEDICA PERUANA 42, no. 2 (2025): 100–110. https://doi.org/10.35663/amp.2025.422.3259.
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Objective: Gallbladder cancer is a relatively uncommon neoplasm of the biliary system, characterized by a notably high mortality rate. Thisstudy aimed to identify prognostic factors for overall survival (OS) in Peruvian patients undergoing surgery for gallbladder cancer. Materials and methods: We conducted a retrospective cohortstudy of patientswith gallbladder carcinoma who underwent surgery at the Instituto Nacional de Enfermedades Neoplásicas between 2000 and 2020. OS was analyzed using the Kaplan–Meier method, and prognostic factors were identified using Cox proportional hazardsregressionmodels. Results: A total of 64 patientswere included. Themedian agewas 62 years, and 75%were female.Most patientswere diagnosed at stage T3 (37.5%), and 25% had M1 stage disease. Additionally, 51.6% of tumors were moderately differentiated, and 71.9% were of the adenocarcinoma histologic subtype. With a median follow-up of 70 months, the 3-year OS rate was 45%. Independent prognostic factorsforOS included AJCC stage, high histological grade (vs. well/moderately differentiated; HR = 2.65, 95% CI: 1.06–6.63), and histologic subtype other than adenocarcinoma (HR = 3.10, 95% CI: 1.21–7.99). Conclusions: Prognostic factors associated with worse OS in Peruvian patients with gallbladder cancer undergoing surgery include AJCC stage, poorly differentiated histological grade, and histologic subtypes other than adenocarcinoma.
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Sivakumar, Smruthy, Jay A. Moore, Meagan Montesion, et al. "Abstract 931: Comprehensive analysis of 3,600 small cell lung cancer cases reveals rare genetic subtypes and multiple mechanisms of histological transformation." Cancer Research 83, no. 7_Supplement (2023): 931. http://dx.doi.org/10.1158/1538-7445.am2023-931.
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Abstract Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with limited treatment options and extremely poor survival outcomes. A major barrier in the field has been the relative paucity of human tumors studied and lack of access to longitudinal samples to understand tumor evolution. Methods: Here we provide a comprehensive analysis of 3,600 patients with SCLC who underwent targeted genomic profiling of at least 324 cancer-related genes as part of routine clinical care, including 678 cases with additional clinical and treatment information obtained from a US-based de-identified SCLC clinico-genomic database that originated from approximately 280 US cancer clinics. This large cohort allowed us to examine for new genetic subtypes, ancestry-associated genomic alterations, biopsy site-specific patterns, survival trends and histological transformation of SCLC from non-small cell lung cancer (NSCLC). Results: Consistent with prior studies, SCLCs were predominantly TP53/RB1 altered. Yet, 5.5% of the cases in our cohort were TP53/RB1 wild-type tumors. These tumors often lacked a tobacco mutational signature, exhibited alternate mechanisms of p53/Rb pathway inactivation (e.g., CDKN2A, CCND1, MDM2), and had a high fraction of human papillomavirus-positive cases (12.7%). Another rare subtype of SCLCs included STK11-altered tumors (1.7%), which were observed more frequently in patients of African ancestry, and were associated with a decreased overall survival (OS) compared with the STK11 wild-type cohort. In our cohort, gene amplifications on 4q12 (KDR, KIT, PDGFRA) were associated with increased OS while CCNE1 amplification was associated with decreased OS. Interestingly, alterations in PTEN were more common in brain metastases compared to lung biopsies and liver metastases, suggesting its potentially unique role in brain metastases of SCLCs. Profiling of over 100 putative transformed SCLCs demonstrated that lineage plasticity may occur at variable lengths of time from the original NSCLC diagnosis and include multiple distinct molecular cohorts of NSCLC, beyond EGFR-mutant NSCLC (e.g., kinase fusion+ tumors: RET, ALK, ROS1, NTRK1). Conclusion: Our work underscores the existence of genetic subtypes in SCLC, including rare subtypes with potential clinical utility. Findings from this study provide an improved understanding of genetic subtypes in SCLC and better inform mechanisms of transformation to SCLC from NSCLC, that may further guide the development of personalized therapies for subsets of patients with this fatal tumor. Citation Format: Smruthy Sivakumar, Jay A. Moore, Meagan Montesion, Douglas I. Lin, Zoe Fleischmann, Ericka M. Ebot, Justin Newberg, Jennifer M. Mills, Priti S. Hegde, Garrett M. Frampton, Julien Sage, Christine M. Lovly. Comprehensive analysis of 3,600 small cell lung cancer cases reveals rare genetic subtypes and multiple mechanisms of histological transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 931.
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Ignatova, A. V., Yu V. Alymov, and I. S. Romanov. "Molecular profile of salivary gland tumors: discovering new targets for therapy." Head and Neck Tumors (HNT) 14, no. 4 (2025): 10–23. https://doi.org/10.17650/2222-1468-2024-14-4-10-23.
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Introduction. Due to variety of morphological subtypes and poor clinical response, comprehensive molecular profiling for salivary gland cancers become a part of treatment strategy for chemotherapy-resistant cases. Tumors of the salivary glands include more than 20 histological types distinguished by their biological characteristics, response to therapy, and prognosis. The search for specific therapeutically significant markers and mutations for various histological types of salivary gland tumors may allow the development of a diagnostic algorithm and improve patient treatment results.Aim. To search for therapeutically significant molecular and genetic targets and immunohistochemical markers in various histological types of malignant salivary gland tumors.Materials and methods. We analyzed data on 280 patients with unresectable recurrent and metastatic salivary gland cancer to identify the main characteristic therapeutically significant immunohistochemical (androgen receptor (AR), epidermal growth factor receptor type 2 (HER2neu), epidermal growth factor receptor (EgfR), programmed cell death receptor 1 (pD-L1) (CpS), сD117, estrogen receptor (ER), progesterone receptor (pR), pan-TRk) and molecular genetic targets (ALK, BRAF, ERBB2, KIT, MET, RET, ROS1, SMO, AR, HRAS, PIK3CA, PDGFRA, NTRK1-3) depending on the histological subtype of the tumor.Results. Based on the results obtained, in comparison with previous studies, a greater diversity of therapeutically significant mutations, fusions and immunohistochemical markers was revealed for various histological types of tumors. Interestingly, increased expression of AR was detected not only in salivary duct carcinoma, but also in carcinoma ex pleomorphic adenoma, adenocarcinoma not otherwise specified, myoepithelial, mucoepidermoid, adenoid cystic, acinic cell, polymorphous adenocarcinomas. ETV6-NTRK3 gene fusions in addition to secretory carcinoma were detected in mucoepidermoid and salivary duct carcinomas. mutations and fusions in the RET gene have been identified in ductal and mucoepidermoid carcinomas, as well as adenocarcinoma not otherwise specified.Conclusion. The results of the study allow to expand the group of patients for molecular genetic and IHC testing in order to individualize therapy.
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Dozic, Slobodan, Dubravka Cvetkovic-Dozic, Milica Skender-Gazibara, and Branko Dozic. "Review of the World Health Organization classification of tumors of the nervous system." Archive of Oncology 10, no. 3 (2002): 175–77. http://dx.doi.org/10.2298/aoo0203175d.
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(Conclusion) Classifications of the nervous system tumors should be neither static nor definitive. The most recent, third, current WHO classification of nervous system tumors was published in 2000. Many substantial changes were introduced. New entities include the chordoid glioma of the third ventricle, the atypical teratoid/rhabdoid tumor, cerebellar liponeurocytoma (the former lipomatous medulloblstoma of the cerebellum), solitary fibrous tumor and perineurioma. The new tumor variants include the large cell medulloblastoma, tanacytic ependymoma and rhabdoid meningioma. Several essential changes were introduced in the meningiomas regarding histological subtypes, grading and proliferation index. In addition to new entities described in the 2000 WHO classification there are newly brain tumor entities and tumor variants, which are not included in the current classification due to the insufficient number of reporeted cases, for example papillary glioneuronal tumor, rosetted glioneuronal tumor, lipoastrocytoma and lipomatous meningioma. They will be probably accepted in the next WHO classificaton. In the current WHO classification the importance of cytogenetic and molecular biologic investigation in the understanding and further classifications of these tumors has been emphasized.
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Gelsomino, Francesco, Giuseppe Lamberti, Marcello Tiseo, et al. "Atezolizumab in a CoHort of pretreated, advanced, non-small cell lung cancer patients with rare HistologiCal SubtypEs (CHANCE trial)." Therapeutic Advances in Medical Oncology 12 (January 2020): 175883592091598. http://dx.doi.org/10.1177/1758835920915983.
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Background: Although immunotherapy with immune-checkpoint inhibitors (ICIs) has profoundly changed the therapeutic scenario in the treatment of advanced non-small cell lung cancer (NSCLC), trials of ICIs only enrolled NSCLC patients with common histology. Atezolizumab was approved by the United States Food and Drug Administration (US FDA) in October 2016 and by the European Medicines Agency (EMA) in September 2017 for the treatment of patients with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression. Methods: We designed a single-arm, multicenter, two-stage phase II study and plan to enroll 43 patients. The primary objective of the study is to evaluate the antitumor activity of atezolizumab in advanced NSCLC patients with rare histology subtypes. Patients with prior atezolizumab or ICI treatment and with untreated, symptomatic, or progressing brain metastases will be excluded. The primary endpoint is disease control rate. Secondary objectives are toxicity and safety, overall response rate, progression-free survival, overall survival, and time to progression. Diagnosis of NSCLC with rare histology will be confirmed by central pathology revision, and will include: colloid carcinoma, fetal adenocarcinoma, non-endocrine large cell carcinoma, sarcomatoid carcinoma, salivary gland-type tumor, lymphoepithelioma-like carcinoma, and NUT-nuclear protein in testis carcinoma. Archival tumor tissue is required for correlative studies of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes. Conclusions: Therapeutic options in NSCLC with rare histology subtypes, to be assessed in specifically designed trials, are an unmet need. This trial will help elucidate the role of atezolizumab as a viable option in this setting.
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Parham, David M., and Petros Giannikopoulos. "Rhabdomyosarcoma: From Obscurity to Clarity in Diagnosis … But With Ongoing Challenges in Management: The Farber-Landing Lecture of 2020." Pediatric and Developmental Pathology 24, no. 2 (2021): 87–95. http://dx.doi.org/10.1177/1093526620977720.
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Rhabdomyosarcoma, the most common soft tissue sarcoma in childhood, has challenged and intrigued soft tissue pathologists ever since the original descriptions. Once based on the identification of rhabdomyoblastic cells with elongate eosinophilic cytoplasm, the diagnosis has evolved to include tumors composed only of primitive mesenchymal cells but now relies heavily on immunohistochemical stains for desmin, myogenin, and MyoD. Rhabdomyosarcomas show a variety of histological patterns, giving rise to classifications that have included embryonal, alveolar, botryoid, pleomorphic, spindle cell, and sclerosing subtypes. These have been linked to prognosis and treatment assignment in the past, but that concept has been superseded by the identification of PAX3-FOXO1 or PAX7-FOXO1 fusions. Fusion testing results are more predictive of outcome and have become standard practice in clinical management. However, high risk tumors with alveolar histology or metastatic disease continue to resist oncologic treatment.
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Ilyas, Sumera I. "Abstract IA21: Molecular Pathogenesis and Cells of Origin of Intrahepatic Cholangiocarcinoma." Clinical Cancer Research 28, no. 17_Supplement (2022): IA21. http://dx.doi.org/10.1158/1557-3265.liverca22-ia21.
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Abstract Intrahepatic cholangiocarcinoma (iCCA) originates in the intrahepatic biliary tree above the second order bile ducts. There are two primary histological subtypes of iCCA: small bile duct iCCAs which arise at the level of the smaller intrahepatic bile ducts, and large bile duct iCCAs which arise in the large intrahepatic bile ducts. Hepatic stem or progenitor cells and cuboidal cholangiocytes are the cells of origin of small bile duct iCCA, whereas large bile duct iCCAs arise from columnar mucous cholangiocytes or peribiliary glands. The molecular pathogenesis of iCCA is distinct from the other anatomic subtypes of CCA. Potentially actionable genomic aberrations that occur in iCCA include fibroblast growth factor receptor 2 (FGFR2) gene fusions, isocitrate dehydrogenase (IDH) 1 and 2 mutations, BRAF mutations, and neutrotrophic tyrosine receptor kinase (NTRK) gene fusions. Epigenetic aberrations that occur in iCCA include inactivating mutations of chromatin remodeling genes such as BAP1 and ARIDIA. Additionally, IDH 1/2 mutations lead to the production of oncometabolites with consequent widespread epigenetic changes. IDH inhibitors and FGFR inhibitors have now received FDA approval for IDH mutated and FGFR altered CCA, respectively. Immune checkpoint inhibition has received tissue agnostic FDA approval for mismatch repair deficient/MSI high CCAs. Other targeted therapies such as PARP inhibitors and CDK4/6 inhibitors are under active investigation. Citation Format: Sumera I Ilyas. Molecular Pathogenesis and Cells of Origin of Intrahepatic Cholangiocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr IA21.
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Xu, Wenyan, and Yanfang Li. "Is Omentectomy Mandatory Among Early Stage (I, II) Malignant Ovarian Germ Cell Tumor Patients? A Retrospective Study of 223 Cases." International Journal of Gynecologic Cancer 27, no. 7 (2017): 1373–78. http://dx.doi.org/10.1097/igc.0000000000001012.
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ObjectiveThe aim of the study was to investigate whether omentectomy (OMT) is necessary in the operation for apparently early stage malignant ovarian germ cell tumors (MOGCTs).Methods and MaterialsSearching medical records database of Sun Yat-sen University Cancer Center from January 1, 1966, to November 30, 2015, patients with MOGCTs were identified and their age, year of diagnosis, tumor grade, histologic subtype, International Federation of Gynecology and Obstetrics stage, nodal findings, gross observation of omentum, and performance of OMT were assessed. Overall survivals of patients with or without OMT were compared using Kaplan-Meier survival curves.ResultsA total of 223 MOGCT cases with clinically early stage (stage I and II) disease and with the 3 common histological subtypes of MOGCT were obtained, which include yolk sac tumor (YST), dysgerminoma (DSG), and immature teratoma (IMT). There were 192 stage I cases and 31 stage II cases. Fifty-four patients were diagnosed with YST, 61 with DSG, and 108 with IMT. Omentectomy was performed as part of the initial surgery in 74.0% patients (165/223) and was omitted in 26.0% patients (58/223). Chemotherapy was administered in 88.3% (197/223) of all patients. The median follow-up was 82.0 months. The 10-year overall survival rates of the patients with and without OMT were 90.5% and 98.1%, respectively (P = 0.156). Regarding different stages or histological subtypes, the 10-year survival rates of the 2 groups were 92.0% versus 97.9% (P = 0.324, stage I), 83.2% versus 100% (P = 0.351, stage II), 89.2% versus 100% (P = 0.303, YST), 94.1% versus 100% (P = 0.470, DSG), and 89.4% versus 96.0% (P = 0.405, IMT), respectively.ConclusionsIn conclusion, OMT in patients with clinically early stage MOGCT may not improve patient survival and may be omitted.
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Kaibysheva, V. O., S. V. Shchelochenkov, T. D. Shchelochenkova, et al. "Eosinophilic gastritis, enteritis, and colitis: understudied subtypes within the spectrum of eosinophilic gastrointestinal disorders. A literature review." Russian Journal of Evidence-Based Gastroenterology 14, no. 2 (2025): 50. https://doi.org/10.17116/dokgastro20251402150.
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Objective. In recent years, several key consensus documents have been published on eosinophilic gastrointestinal disorders (EGIDs). This review aims to analyze the literature and discuss core concepts, including terminology and classification, etiology, pathogenesis, and treatment of eosinophilic gastritis, enteritis, and colitis. Key points. Eosinophilic gastrointestinal disorders are a group of immune-mediated diseases of unknown etiology, characterized by eosinophilic infiltration of the walls of hollow gastrointestinal organs—from the mucosa to the serosa—resulting in significant clinical symptoms, endoscopic findings, and, in some cases, complications such as perforation, bleeding, ascites, or intestinal obstruction. The first consensus document on EGIDs (2022) proposed standardized nomenclature based on the affected site: eosinophilic esophagitis, eosinophilic gastritis, eosinophilic enteritis, and eosinophilic colitis. The clinical presentation is highly variable and non-specific, depending on the depth of inflammation (mucosal, muscular, or serosal). Validated endoscopic criteria for eosinophilic involvement of the stomach and intestines are not currently available. Diagnosis of eosinophilic gastritis, enteritis, or colitis is based on clinical presentation, endoscopic findings, and multifocal mucosal biopsy followed by histological evaluation. There are no established treatment guidelines; empiric approaches include systemic and topical glucocorticoids, biologic therapies, and elimination diets. Conclusion. The diagnosis of eosinophilic gastric and intestinal diseases remains challenging due to non-specific clinical and endoscopic features and the absence of clear histopathological criteria. These conditions are rare and not widely recognized in clinical practice. Current treatment strategies include dietary therapy, corticosteroids, and targeted biologic agents.
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Carreras, Joaquim. "Celiac Disease Deep Learning Image Classification Using Convolutional Neural Networks." Journal of Imaging 10, no. 8 (2024): 200. http://dx.doi.org/10.3390/jimaging10080200.
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Celiac disease (CD) is a gluten-sensitive immune-mediated enteropathy. This proof-of-concept study used a convolutional neural network (CNN) to classify hematoxylin and eosin (H&E) CD histological images, normal small intestine control, and non-specified duodenal inflammation (7294, 11,642, and 5966 images, respectively). The trained network classified CD with high performance (accuracy 99.7%, precision 99.6%, recall 99.3%, F1-score 99.5%, and specificity 99.8%). Interestingly, when the same network (already trained for the 3 class images), analyzed duodenal adenocarcinoma (3723 images), the new images were classified as duodenal inflammation in 63.65%, small intestine control in 34.73%, and CD in 1.61% of the cases; and when the network was retrained using the 4 histological subtypes, the performance was above 99% for CD and 97% for adenocarcinoma. Finally, the model added 13,043 images of Crohn’s disease to include other inflammatory bowel diseases; a comparison between different CNN architectures was performed, and the gradient-weighted class activation mapping (Grad-CAM) technique was used to understand why the deep learning network made its classification decisions. In conclusion, the CNN-based deep neural system classified 5 diagnoses with high performance. Narrow artificial intelligence (AI) is designed to perform tasks that typically require human intelligence, but it operates within limited constraints and is task-specific.
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Yassen Kadhim, Hala, Thekra Atta Ibrahim, and Ali Hafedh Abbas. "Histological and histopathological structural changes in the skin of the Basal Cells Carcinoma patients." Diyala Journal of Medicine 27, no. 1 (2024): 75–85. http://dx.doi.org/10.26505/djm.v27i1.1143.
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Background: Basal Cell Carcinoma (BCC) is the most common type of skin carcinoma and is considered an epidemic disease due to its increasing frequency in many countries. The most important problem of BCC is local invasion It grows in a “silent” way into immediately adjacent tissue. It rarely metastasizes. The early tumors are commonly small, translucent or pearly, raised and rounded areas located on a few dilated, superficial vessels. There are six subtypes of BCC that include nodular, pigmented, superficial, morphea form, cystic. The most important risk factor for basal cell carcinoma is exposure to UV-radiation. Outdoor workers with a long history of work-related UV-exposure are at increased risk of developing BCC. Other risk factors include family history of skin carcinoma, light skin phototypes, advanced age. Objective: The current study investigated pathological and histological changes in tissue sections to identify the factors contributing to the infection frequency. Patients and Methods: Thirty-three BCC patients' samples have been collected from the main care center at al-Baquba Teaching Hospital of Diyala Province, Iraq. All patient groups were clinically diagnosed as BCC by dermatologists. Results: The study showed macroscopic and microscopic histological changes. An ulcerated macroscopic appearance of the lesion was shown. The tumor lesions are located on the face. It was noted that the percentage of patients was higher in men than women and higher in light skin than dark skin. The study also showed that the age group 66-74 years had a higher infection percentage, while the lower percentage was of the age group > 83 years. Conclusion: These findings pave the way for future research endeavors aimed at prevention, early detection, and targeted treatment strategies for this prevalent skin carcinoma. Keywords: Basal Cell Carcinoma, skin tumor, non-melanoma skin cancer
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Marchetti, Andrea, Matteo Rosellini, Veronica Mollica, et al. "The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory?" International Journal of Molecular Sciences 22, no. 12 (2021): 6237. http://dx.doi.org/10.3390/ijms22126237.
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Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.
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Afzal, Muhammad Zubair, and Linda T. Vahdat. "Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine." Journal of Personalized Medicine 14, no. 7 (2024): 719. http://dx.doi.org/10.3390/jpm14070719.
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Breast cancer is the most common cancer among women in the world as well as in the United States. Molecular and histological differentiation have helped clinicians optimize treatments with various therapeutics, including hormonal therapy, chemotherapy, immunotherapy, and radiation therapy. Recently, immunotherapy has become the standard of care in locally advanced triple-negative breast cancer and an option across molecular subtypes for tumors with a high tumor mutation burden. Despite the advancements in personalized medicine directing the management of localized and advanced breast cancers, the emergence of resistance to these therapies is the leading cause of death among breast cancer patients. Therefore, there is a critical need to identify and validate predictive biomarkers to direct treatment selection, identify potential responders, and detect emerging resistance to standard therapies. Areas of active scientific and clinical research include novel personalized and predictive biomarkers incorporating tumor microenvironment, tumor immune profiling, molecular characterization, and histopathological differentiation to predict response and the potential emergence of resistance.
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Uhlig, Johannes, Annemarie Uhlig, Hari Anant Deshpande, Michael E. Hurwitz, Peter Humphrey, and Kevin Kim. "Renal sarcomas: Epidemiology, treatment and outcomes." Journal of Clinical Oncology 39, no. 6_suppl (2021): 362. http://dx.doi.org/10.1200/jco.2021.39.6_suppl.362.
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362 Background: Renal sarcomas are a rare malignancy in adults and have been inadequately evaluated on a US national level regarding epidemiology, treatment, and outcomes. Methods: The 2004-2016 NCDB and SEER databases were queried for adult patients diagnosed with sarcomas of renal origin. Age-adjusted incidence rates were derived from the SEER database. Overall survival (OS) was assessed using multivariable Cox proportional hazards models adjusting for demographics, tumor and treatment variables. Results: 1,279 renal sarcomas comprising 39 subtypes were reported from 2004-2016, contributing 0.3% of all NCDB renal malignancies. As shown in the table below, the most common subtypes were leiomyosarcoma (LMS), angiosarcoma (AS), malignant rhabdoid tumor (MRT), dedifferentiated liposarcoma (DL) and primitive neuroectodermal tumors (PNET). Over the study period, renal sarcoma incidence rates remained constant at 0.5 cases / 1 million citizens. Sex-specific incidence differences were evident with female predominance for LMS, and male predominance for AS. Age at diagnosis and tumor diameter varied according to sarcoma subtypes: for example, median age in LMS was 62y compared to 30y in Ewing sarcoma patients; median tumor diameter was 18cm for solitary fibrous tumors and 7.5cm for synovial sarcoma. Renal sarcoma was staged as T3 in 33.3% and T4 in 14.2%, while distant metastases were evident in 29.1% of cases at diagnosis. Most T1-T3 stage renal sarcomas underwent surgical resection (992/1098, 84%), compared to 71% for T4 renal sarcomas (128/181). Systemic therapy was administered in 32.1% of renal sarcoma cases (23.5% combined with surgical resection). Renal sarcoma 1-,2-, and 5-year OS rates were 48%, 24%, and 13%. OS was worse for T4 vs T1-3 sarcomas (HR=1.6, p<0.001), and cases with distant metastases vs none (HR=3.2, p<0.001). As summarized in the table, OS varied according to sarcoma subtypes with worse OS for AS compared to PNET (HR=1.5, p=0.04). Conclusions: Accounting for 0.3% of renal malignancies in adults, renal sarcomas include 39 different histological subtypes with distinct demographics, tumor parameters and outcomes. Renal sarcomas commonly present with advanced T stage at diagnosis and are treated with surgical resection with or without systemic therapy. [Table: see text]
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Chu, Yanshuo, Kyung Serk Cho, Isha Khanduri, et al. "Abstract 7417: SpatialCS: A tool to effectively integrate histological annotations and spatial transcriptomics analysis." Cancer Research 84, no. 6_Supplement (2024): 7417. http://dx.doi.org/10.1158/1538-7445.am2024-7417.
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Abstract Spatial transcriptomics is revolutionizing our understanding of tumor ecosystems, providing insights into the spatial dimensions of cell locations, their organization, and interactions within tissues. A key challenge in this field is integrating histological annotations with spatial domains identified through unsupervised clustering methods like SpaGCN. This integration is crucial for accurate spatial domain identification and further analyses. However, clustering results often vary based on parameters such as resolution, leading to inconsistencies with histological annotations. This variation necessitates optimized parameter selection to achieve the best clustering outcomes. We here introduce SpatialCS, a novel tool specifically designed to both visualize and quantify the alignment between histological annotations and the clustering results obtained from spatial transcriptomics data. SpatialCS employs a new index based on the asymmetric Wallace indices. This index penalizes spot pairs that are clustered together but do not share the same histology annotation type, with penalties scaled according to their transcriptional similarity. Additionally, we propose a purity index, derived by calculating the average transcriptional entropy of all clusters. This index serves as a measure of the homogeneity within each cluster. Furthermore, SpatialCS includes a unique visualization function. This function projects histological annotations onto the clustering results as outlines, making it easier to assess the consistency between histology annotations and clustering outcomes. We have applied SpatialCS to Visium spatial transcriptomics data generated on four colorectal cancer liver metastases, each accompanied by comprehensive spot-level histological annotations in both tumor and normal compartments. The histologic annotations include but not limited to are tumor cells, tumor cell cluster subtypes, tumor stroma, tumor in the vessels, portal tract, individual bile ducts, portal vein and liver cell plates and non-neoplastic stroma. The application of SpatialCS has proven its effectiveness in identifying the most consistent clustering results, which were further confirmed by experienced pathologists. Notably, the output of SpatialCS offers helpful guidance for improving histological annotations. Together, SpatialCS not only provides a quantitative approach to evaluate the consistency between histological annotations and unsupervised clustering analysis but also showcases its potential to significantly enhance histological annotations. Citation Format: Yanshuo Chu, Kyung Serk Cho, Isha Khanduri, Tieling Zhou, Jiahui Jiang, Yunhe Liu, Xinmiao Yan, Guangsheng Pei, Yibo Dai, Yang Liu, Ruiping Wang, Akshaya S Jadhav, Sharia Hernandez, Humam Kadara, Luisa Maren Solis Soto, Scott Kopetz, Dipen Maheshbhai Maru, Linghua Wang. SpatialCS: A tool to effectively integrate histological annotations and spatial transcriptomics analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7417.
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Banson, Mabel, Felix Siaw-Debrah, Kwadwo Darko, Mawuli Ametefe, and Patrick Bankah. "OTHER-06 EPIDEMIOLOGY OF BRAIN AND SPINE TUMOURS – A SINGLE CENTRE DESCRIPTIVE RETROSPECTIVE STUDY." Neuro-Oncology Advances 5, Supplement_4 (2023): iv7. http://dx.doi.org/10.1093/noajnl/vdad121.027.
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Abstract Brain and spine tumours are of significant public health concern and lead to severe morbidities and mortalities. The incidence is on the rise, ranking as the fifth (5th) leading cause of cancer-related deaths in Africa. Treatment and prognosis depend on age, tumour location, functional neurological status, extent of tumour resection and histological subtype of tumour. This study aims to describe the patient demographics, clinical presentation, and histological subtypes of central nervous system (CNS) tumours in the Korle-Bu Teaching Hospital. A retrospective review of the medical records and histopathology reports (reports presented to the unit) of all patients with CNS tumours operated upon in the Neurosurgical Unit, Department of Surgery, Korle-Bu Teaching Hospital over the past 17years (2007-2023) was collated. The patients without definitive histopathological diagnosis were excluded from the study. Epidemiological data retrieved include clinical presentation, histological subtype, patient age and sex and the spatial distribution. A total of 327 tumour were recorded in the Neurosurgery unit: 85.3% were Brain Tumours. 178 (54.4%) were females and 149 (45.6%) males. Overall Meningiomas were the commonest CNS tumour encountered forming 32.1% followed by Gliomas, Glioneuronal and Neuronal tumours with 29.4% then Tumours of the Sella region, 19.6%. The commonest Meningioma subtype was Meningothelial (33%). Of the Gliomas, Low grade gliomas formed 69%. The commonest symptom for brain cases were headaches (59.1%) followed by visual impairment (33.0%). Of the spine cases, the prevalent symptom was paraparesis (46.2%) followed with low back pain and bowel and bladder dysfunction at 23.1% respectively. We concluded that Low grade tumours predominate in our setting. It is prudent that we channel efforts towards prompt diagnosis and treatment of such cases.
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Ortonne, Nicolas, Steven L. Carroll, Fausto J. Rodriguez, et al. "Assessing interobserver variability and accuracy in the histological diagnosis and classification of cutaneous neurofibromass." Neuro-Oncology Advances 2, Supplement_1 (2019): i117—i123. http://dx.doi.org/10.1093/noajnl/vdz050.
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Abstract Background Cutaneous neurofibromas (cNFs) are the most common tumors in people with neurofibromatosis type 1 (NF1) and are associated with reduced quality of life. There is currently no widely accepted standardized language for describing cNFs clinically or histopathologically. The objective of this study was to evaluate interobserver agreement across pathologists in describing and reporting of neurofibromas involving the skin. Methods Twenty-eight (H&E)-stained slides of cNF were scanned using an Aperio XT scanner. The digital images were reviewed by 6 pathologists, who entered free text of up to a 200 word description for each case into a REDcap database. Responses were analyzed for the most commonly used terms based on frequency, as well as agreement (reported as concordance) between reviewers. Results A set of the terms most commonly used by pathologists for the histological classification of cNF along with areas of agreement and disagreement have been identified. The study shows that there was strong agreement across reviewers that not all neurofibromas involving the skin are cutaneous neurofibromas and regarding the presence or absence of atypical features and heterologous elements. Areas of less concordance were identified and include cNF subtypes, definition of extension and pattern of growth, as well as the distinction of a cNF from a plexiform without an intraneural component involving skin. Conclusions This work is the first step towards development of a robust classification system and devising “gold standard” histopathologic diagnostic criteria for cutaneous neurofibromas.
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Ang, Celina, Aatur D. Singhi, Alexa Betzig Schrock, et al. "Comprehensive genomic sequencing of appendiceal cancer tumors to identify different genomic alterations by subtype, novel treatment opportunities, and improved outcomes." Journal of Clinical Oncology 35, no. 4_suppl (2017): 599. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.599.
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599 Background: Appendiceal cancers are rare and consist of mucinous (M), adenocarcinoma (A), goblet cell carcinoma (GCC), pseudomyxoma peritonei (PMP), and several even rarer histologies. Current treatment involves surgical resection or debulking; no standard exists for adjuvant chemotherapy or metastatic disease treatment. Systemic treatment is often based on chemotherapy regimens used in colorectal cancer. Methods: Tissue from 518 appendiceal cancer patients was assayed by hybrid-capture based comprehensive genomic profiling (CGP) in the course of clinical care to evaluate genomic alterations (GA: base substitutions, indels, amplifications, copy number alterations, fusions/rearrangements) and targeted therapy opportunities; 315 genes frequently altered in cancer were assayed. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb sequenced DNA and reported as mutations/Mb. Results: Profiling across all appendiceal cancer histological subtypes identified different patterns in GAs across subtypes (table), most notably in GNAS, KRAS, and TP53. No PMP exhibited microsatellite instability (MSI-H) or high TMB ( > 20 mutations/Mb); MSI-H cases included 3 M, 4 A, 1 GCC; 3-7% 12% A and 6% m had high TMB. Case reports of patients with tumors harboring GNAS alterations showed response to MEK inhibitors. Conclusions: Genomic profiles of tumors from patients with appendiceal cancers reveal differing profiles from colorectal cancers (CRC) and considerable heterogeneity between subtypes, suggesting an individualized approach to treatment. Therapeutic options include clinical trials targeting pathways involving KRAS, BRAF, GNAS, PIK3CA, FBXW7, SMAD4, APC, and ATM. Recent case reports indicate that GNAS is a clinical target for MEK inhibitors. Overall, given the poor prognosis of advanced stage appendiceal carcinoma patients, CGP may identify novel, unanticipated therapeutic targets in a significant subset of patients, including immunotherapy for high TMB patients. [Table: see text]
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Paraskevaidi, Maria, Camilo L. M. Morais, Olivia Raglan, et al. "Spectroscopy of blood samples for the diagnosis of endometrial cancer and classification of its different subtypes." Journal of Clinical Oncology 35, no. 15_suppl (2017): 5596. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5596.
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5596 Background: Symptoms of endometrial cancer often appear in early stages, thus a diagnosis, based on microscopic histological examination of endometrial tissue, can be given relatively on time. However, this procedure interferes subjective interpretation allowing human error, while screening of the asymptomatic population is not widely performed because of the high cost of the available tests (e.g. transvaginal ultrasound) and the relative invasiveness [biopsy or dilation and curettage (D+C)]. Consequently, there is a widespread need to develop inexpensive, non-invasive techniques that would accurately diagnose endometrial cancer, as well as classify the different subtypes. Spectrochemical methods generate a signature fingerprint of biological material in the form of spectra. Unlike immunological methods, which detect only one molecule at a time, the spectra obtained from a clinical sample represent all the molecular constituents within that sample, including proteins, lipids and carbohydrates; this provides a holistic picture of the sample. Previous studies have confirmed spectroscopy’s ability to diagnose gynecologic cancers in blood. Methods: Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyse blood plasma and serum from 71 women with endometrial cancer and 18 age-matched healthy controls; classification algorithms were then applied to extract the underlying biological information. Results: Principal component analysis followed by support vector machine (PCA-SVM) diagnosed endometrial cancer with 100% accuracy in plasma and 95% in serum. Discrimination between the different subtypes [endometrioid adenocarcinoma (n = 43) vs carcinosarcoma (n = 14)] was achieved with 98.33% accuracy in both plasma and serum. The spectral regions responsible for discrimination were attributed to protein and lipid alterations. Conclusions: Our preliminary results suggest an accurate and objective diagnostic tool for endometrial cancer with blood testing, allowing therefore thoughts for a potential screening test in high risk populations. Future work will include higher number of normal cases and different subtypes and grades.
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Takahashi, Yoshihisa, Erdenetsogt Dungubat, Hiroyuki Kusano, et al. "Application of Immunohistochemistry in the Pathological Diagnosis of Liver Tumors." International Journal of Molecular Sciences 22, no. 11 (2021): 5780. http://dx.doi.org/10.3390/ijms22115780.
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Although radiological diagnostics have been progressing, pathological diagnosis remains the most reliable method for diagnosing liver tumors. In some cases, definite pathological diagnosis cannot be obtained by histological evaluation alone, especially when the sample is a small biopsy; in such cases, immunohistochemical staining is very useful. Immunohistochemistry is the most frequently used technique for molecular pathological diagnosis due to its broad application, ease of performance and evaluation, and reasonable cost. The results occasionally reflect specific genetic mutations. The immunohistochemical markers of hepatocellular carcinoma include those of hepatocellular differentiation—such as hepatocyte paraffin 1 and arginase-1—and those of malignant hepatocytes—such as glypican-3, heat shock protein 70, and glutamine synthetase (GS). To classify the subtypes of hepatocellular adenoma, examination of several immunohistochemical markers, such as liver fatty acid-binding protein, GS, and serum amyloid A, is indispensable. Immunohistochemical staining for GS is also important for the diagnosis of focal nodular hyperplasia. The representative immunohistochemical markers of intrahepatic cholangiocarcinoma include cytokeratin (CK) 7 and CK19. In this article, we provide an overview of the application of immunohistochemistry in the pathological diagnosis of liver tumors referring to the association with genetic alterations. Furthermore, we aimed to explain the practical points in the differential diagnosis of liver tumors by immunohistochemical staining.
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Novikova, V. P., A. I. Khavkin, and N. E. Prokopyeva. "IBD-like gastrointestinal disorders in children." Experimental and Clinical Gastroenterology, no. 4 (July 21, 2021): 161–69. http://dx.doi.org/10.31146/1682-8658-ecg-188-4-161-169.
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Traditionally, inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD). At the same time, there are a number of lesions of the gastrointestinal tract, which can proceed for a long time under the guise of IBD, masking the true cause of the disease. This leads to late diagnosis and, quite often, fatal consequences. These diseases include autoimmune enteropathy (AIE). It is a fairly rare disease characterized by severe diarrhea and immune- mediated damage to the intestinal mucosa.The aim is to describe the criteria of diagnosis, etiology, pathogenesis, epidemiology, clinic and treatment of AIE in children based on an analysis of modern literature.Results. Diagnostic criteria for AIE include chronic diarrhea (lasting more than 6 weeks), malabsorption syndrome, specific histological findings from small bowel biopsy with the exclusion of other causes of villous atrophy. An additional criterion is the presence of antibodies against enterocytes or goblet cells. There are: (1) AIEs associated with syndromes such as IPEX and APECED; (2) an isolated form of GI AIE with antibodies against enterocytes without diseases of the digestive system; and (3) any form of AIE in girls associated with any other autoimmune phenomena. To date, at least five subtypes of AIE are known: Primary AIE (pediatric); Syndromic AIE (pediatric); Primary (sporadic) EIA of adults; Secondary (iatrogenic) AIE of adults; Paraneoplastic AIE. Patients with AIE may have associated autoimmune diseases, including diabetes mellitus, autoimmune hepatitis, alopecia, hypothyroidism, and interstitial nephritis. AIE. is a complex disease and potentially life-threatening, the mortality rate reaches 30% in pediatric practice. The prognosis depends on the age of onset of the disease, the severity of symptoms and the degree of histological damage to the gastrointestinal tract. Along with nutritional support, immunosuppressive therapy, the use of therapy based on modern knowledge in the field of molecular biology can help control the disease.